Javier Arredondo Montero1, Carlos Bardají Pascual1, Giuseppa Antona1, Mónica Bronte Anaut2, Natalia López-Andrés3, Nerea Martín-Calvo4,5. 1. Pediatric Surgery Department, Hospital Universitario de Navarra, Pamplona, Spain. 2. Pathology Department, Hospital Universitario de Navarra, Pamplona, Spain. 3. Cardiovascular Translational Research, NavarraBiomed (Miguel Servet Foundation), Hospital Universitario de Navarra, Universidad Pública de Navarra (UPNA), IdiSNA, Pamplona, Spain. 4. School of Medicine, Department of Preventive Medicine and Public Health, University de Navarra, Calle Irunlarrea 1, 31008, Pamplona, Navarra, Spain. nmartincalvo@unav.es. 5. IdiSNA, Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain. nmartincalvo@unav.es.
Abstract
BACKGROUND: Pediatric acute appendicitis (AA) is a challenging pathology to diagnose. In the last decades, multiple biomarkers have been evaluated in different human biological samples to improve diagnostic performance. This study aimed to examine the diagnostic performance of serum, fecal and urinary calprotectin as well as the role of the APPY-1 biomarker panel in pediatric acute appendicitis. METHODS: We conducted a systematic review of the literature that involved an extensive search in the main databases of medical bibliography (Medline, PubMed, Web of Science and SciELO). Two independent reviewers selected the relevant articles based on the previously defined inclusion and exclusion criteria. Methodological quality of the selected article was rated using the QUADAS2 index. Data extraction was performed by two independent reviewers. A synthesis of the results, a standardization of the metrics and two random-effect meta-analyses, one for serum calprotectin and one for APPY-1, were performed. RESULTS: The research resulted in 173 articles. Thirty-eight duplicates were removed. Among the remaining 135 articles, we excluded 125 following the inclusion and exclusion criteria, resulting in the 10 studies included in this review. This systematic review included data from of 3901 participants (1276 patients with confirmed diagnosis of AA and 2625 controls). The age of the participants ranged from 0 to 21 years. Four of the studies compared serum calprotectin values and reported significant differences between groups, but inconsistent results regarding cutoff points, sensitivity and specificity. Two publications compared urinary values of calprotectin and presented inconsistent results regarding sensitivity and specificity as well. One publication evaluated the diagnostic performance of fecal calprotectin, but it did not provide data on measured values. Four studies evaluated the diagnostic performance of APPY-1 test in pediatric acute appendicitis. The calculated pooled sensitivity and specificity of those studies were 97.37 (95% CI 95.60-98.44) and 36.74 (95% CI 32.28-41.44), respectively, and the calculated pooled NLR, 0.0714 (95% CI 0.041-0.115). CONCLUSION: Serum calprotectin has limited diagnostic yield in pediatric acute appendicitis. Its performance seems to increase with the hours of clinical evolution and in advanced AA, although the evidence is limited. There is not enough evidence on the usefulness of urinary or fecal calprotectin in the diagnosis of pediatric acute appendicitis. On the other hand, the APPY-1 is a reliable test to exclude the diagnosis of AA in patients at low or moderate risk according to PAS and Alvarado Score.
BACKGROUND: Pediatric acute appendicitis (AA) is a challenging pathology to diagnose. In the last decades, multiple biomarkers have been evaluated in different human biological samples to improve diagnostic performance. This study aimed to examine the diagnostic performance of serum, fecal and urinary calprotectin as well as the role of the APPY-1 biomarker panel in pediatric acute appendicitis. METHODS: We conducted a systematic review of the literature that involved an extensive search in the main databases of medical bibliography (Medline, PubMed, Web of Science and SciELO). Two independent reviewers selected the relevant articles based on the previously defined inclusion and exclusion criteria. Methodological quality of the selected article was rated using the QUADAS2 index. Data extraction was performed by two independent reviewers. A synthesis of the results, a standardization of the metrics and two random-effect meta-analyses, one for serum calprotectin and one for APPY-1, were performed. RESULTS: The research resulted in 173 articles. Thirty-eight duplicates were removed. Among the remaining 135 articles, we excluded 125 following the inclusion and exclusion criteria, resulting in the 10 studies included in this review. This systematic review included data from of 3901 participants (1276 patients with confirmed diagnosis of AA and 2625 controls). The age of the participants ranged from 0 to 21 years. Four of the studies compared serum calprotectin values and reported significant differences between groups, but inconsistent results regarding cutoff points, sensitivity and specificity. Two publications compared urinary values of calprotectin and presented inconsistent results regarding sensitivity and specificity as well. One publication evaluated the diagnostic performance of fecal calprotectin, but it did not provide data on measured values. Four studies evaluated the diagnostic performance of APPY-1 test in pediatric acute appendicitis. The calculated pooled sensitivity and specificity of those studies were 97.37 (95% CI 95.60-98.44) and 36.74 (95% CI 32.28-41.44), respectively, and the calculated pooled NLR, 0.0714 (95% CI 0.041-0.115). CONCLUSION: Serum calprotectin has limited diagnostic yield in pediatric acute appendicitis. Its performance seems to increase with the hours of clinical evolution and in advanced AA, although the evidence is limited. There is not enough evidence on the usefulness of urinary or fecal calprotectin in the diagnosis of pediatric acute appendicitis. On the other hand, the APPY-1 is a reliable test to exclude the diagnosis of AA in patients at low or moderate risk according to PAS and Alvarado Score.